JP2005187412A - Method for producing hard capsule - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a production method for obtaining a hard capsule free from leakage of a liquid by packing a temperature-controlled packing material into the hard capsule for packing a medicine, a health food, a food, and the like, containing cellulose ethers as a base and sealing the capsule with a sealing agent. <P>SOLUTION: The method for producing the hard capsule containing cellulose ethers as the base comprises packing a heated liquid packing material into the hard capsule containing cellulose ethers as the base and sealing fitting parts of the body part and the cap part of the capsule with the sealing agent. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a hard capsule that does not leak by filling a temperature-controlled filling into a filling capsule of a pharmaceutical, health food, food, etc. based on cellulose ethers, and sealing with a sealing agent The present invention relates to a manufacturing method for obtaining

As is well known, hard capsules for pharmaceuticals and health foods are usually based on gelatin, and a film composition in which a plasticizer such as glycerin or sorbitol is added thereto, and if necessary, an opacifying agent, a dye or a pigment is appropriately added and blended. Molded from things. And this thing has about 10-15 mass% water | moisture content normally in this capsule membrane | film | coat.
When the moisture content in the capsule film is 10% by mass or less, the plasticity of the film is lost, the impact resistance during the filling operation of the drug into the capsule is remarkably impaired, and it cannot be used. Therefore, in such a known gelatin hard capsule, it is essential to keep a certain amount of moisture in the film as described above.

However, this gelatin hard capsule contains two or more kinds of drugs that interact with each other in the presence of moisture when the drug filled therein is susceptible to hydrolysis due to moisture in the film. In such a case, the main drug may be decomposed to cause inconveniences such as a decrease in the potency of the main drug, alteration, discoloration, and insolubilization of the capsule film.
In addition, gelatin used as a hard capsule base is an animal protein, and in recent years, a hard capsule that replaces the gelatin capsule has been demanded from the viewpoint of the risk of infection with mad cow disease.

In order to eliminate such drawbacks, various improvements and proposals have been made for hard pharmaceutical capsules. For example, Patent Document 1 uses a water-soluble cellulose ether in which some or all of the hydroxyl groups of cellulose are substituted with alkyl groups or hydroxy groups as a base, and a film is formed by immersing a molding pin in this water-soluble immersion liquid. Discloses a method for producing hard capsules. Patent Documents 2 and 3 disclose a method of blending polyvinyl alcohol (PVA) with the water-soluble cellulose ether and obtaining a hard capsule from the water-soluble immersion liquid. Further, Patent Document 4 discloses a hard capsule for pharmaceuticals comprising a cellulose ether substituted with an alkyl group and a hydroxyalkyl group or a hydroxyalkyl group as a base, and a gelling agent and a gelling aid added thereto. ing. However, these known documents do not describe a sealing method effective for preventing liquid leakage of hard capsules based on cellulose ethers and hard capsules without liquid leakage.
Japanese Patent Publication No. 47-4310 Japanese Patent Laid-Open No. 61-1000051 Japanese Patent Laid-Open No. 62-266060 Japanese Patent No. 2552937

  After filling medicines, health foods, etc. into hard capsules based on cellulose ethers, to produce hard capsules that do not leak, the fitting part between the hard capsule body and cap part is effectively An object of the present invention is to provide a method for obtaining a desired hard capsule by sealing.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors filled a hard capsule based on cellulose ether with a liquid filler, and sealed the sealing part between the body part of the capsule and the fitting part of the cap part. When sealing with, it is surprising that by using a warmed filler, and in this case, preferably by sealing the fitting part with a temperature-controlled sealing agent, The present invention was completed by finding that no hard capsule was obtained. In general, when a liquid as a filling is heated, the viscosity of the liquid decreases and the fluidity increases, and the risk of liquid leakage from the filled capsule is expected to increase. However, in the hard capsule obtained by the method of the present invention, Unexpectedly, such liquid leakage is remarkably suppressed.

That is, the present invention
(1) A hard capsule based on cellulose ethers is filled with a heated liquid filling, and then the body and cap of the capsule are sealed with a sealing agent. A method for producing a hard capsule based on cellulose ethers,
(2) The method for producing a hard capsule according to (1) above, wherein the heating is adjusted so that the temperature of the liquid filling is 30 to 45 ° C.
(3) The method for producing a hard capsule according to (1) above, wherein the heating is adjusted so that the temperature of the liquid filling is 35 to 40 ° C.
(4) The method for producing a hard capsule according to any one of the above (1) to (3), wherein the sealant contains cellulose ethers,
(5) The method for producing a hard capsule according to any one of the above (1) to (4), wherein the sealing agent further contains a hydrophilic solvent and water,
(6) The above-mentioned (1) to (1), wherein the sealing agent contains 10 to 25% cellulose ethers, 45 to 60% alcohols and 15 to 45% water by mass% with respect to the whole sealing agent. 5) The method for producing a hard capsule according to any one of
(7) The method for producing a hard capsule according to any one of the above (1) to (6), wherein the temperature of the sealing agent is 23 to 45 ° C,
(8) The temperature of the liquid filler is 30 to 45 ° C, and the temperature of the sealing agent is 23 to 45 ° C, The hard capsule according to any one of (1) to (7) above Production method,
(9) A hard capsule that can be produced by the method according to any one of (1) to (8) above,
(10) A liquid capsule filled with a liquid filler in a hard capsule based on cellulose ethers, and the fitting part of the capsule body and cap is sealed with a sealing agent containing cellulose ethers. Not hard capsules,
(11) A sealing agent for hard capsules containing 10 to 25% of cellulose ethers, 45 to 60% of alcohols and 15 to 45% of water with respect to the whole sealing agent,
About.

  The method for producing a hard capsule based on the cellulose ethers of the present invention can provide a hard capsule free from leakage or contamination of the liquid filler to the outside of the hard capsule, and waste due to product defects. In addition to the reduction, the manufacturing process management is facilitated, so that the manufacturing time and cost are reduced and it is suitable for large-scale mass production. In particular, even in the case of a low-viscosity filler, liquid leakage after filling can be suppressed by controlling the filler, preferably the sealing agent to a specific temperature range. As a result, it is possible to effectively prevent liquid leakage of the hard capsule obtained by filling the hard capsule based on cellulose ether with the filler. In addition, the hard capsules manufactured by the method of the present invention have excellent operability, and can be transferred normally and smoothly without causing liquid leakage without special measures for transfer and transfer. is there.

  The hard capsules for medicines, health foods and foods used in the present invention are produced in accordance with the usual immersion molding method as well as known gelatin hard capsules or cellulose ether hard capsules (for example, see Patent Document 4). . That is, cellulose ethers are used as a hard capsule base, and a gelling agent (for example, carrageenan, pectin) and a gelling aid (for example, potassium ion, ammonium ion, etc.) are appropriately blended as necessary, and a hard capsule base aqueous solution. (Immersion solution) is prepared, and an immersion molding pin is immersed in the aqueous solution, and a hard capsule film is obtained according to a conventional method. In this manufacturing process, the body part and the cap part of the hard capsule can be respectively obtained by the size of the immersion molding pin. In FIG. 1, the manufacturing process of the hard capsule of this invention is typically shown and shown.

  Here, the hard capsule base aqueous solution is generally about 5 to 25% cellulose ether, about 74 to 94% water, about 0.05 to 0.5% gelling agent, and about 0. 01 to 0.5%, and if necessary, may be prepared by appropriately blending a colorant (for example, titanium oxide, bengara, blue No. 2, yellow No. 5, etc.), an opacifier (titanium oxide etc.), a perfume and the like. it can.

  Cellulose ethers that are hard capsule bases include, for example, alkyl cellulose (for example, methyl cellulose), hydroxyalkyl cellulose (for example, hydroxyethyl cellulose, hydroxypropyl cellulose), hydroxyalkyl alkyl cellulose (for example, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, Hydroxyethyl ethyl cellulose) or a mixture thereof is exemplified. Of these, hydroxyalkylalkylcellulose is preferred, and specifically, hydroxypropylmethylcellulose is exemplified as a preferred base.

  The body part and the cap part of the cellulose ether hard capsule thus obtained are filled with a liquid filling material, and then the body part is covered with the cap part to fit the body part and the cap part. Next, the sealing agent is applied to the surface of the body part and the surface of the cap part with a constant width centering on the edge of the cap part, and preferably once to a plurality of times in the circumferential direction of the body part and the cap part, preferably The fitting part is sealed by applying once or twice. In this case, it is preferable that the temperature of the filler and the sealant, particularly the filler, is controlled within a certain temperature range as described below.

  As the size of the hard capsule, there are 00, 0, 1, 2, 2, 3, 4, 5, etc., but any size of hard capsule can be used in the present invention.

  Examples of the filling material to be filled in the hard capsule of the present invention include pharmaceuticals and health foods, and any of them can be filled as long as it does not dissolve or react with the hard capsule film of cellulose ethers. Liquid medicine, health food, food, etc. In addition, it is not always necessary to be liquid at room temperature (usually 15 to 25 ° C.) as long as the filling can be heated to be in a liquid or gel state when filling the hard capsule.

The liquid filling to be filled in the hard capsule of the present invention is not particularly limited as long as it is not toxic when used as a pharmaceutical, health food or food. For example, alcohols and polyhydric alcohols include stearyl alcohol, cetanol, polyethylene glycol 600, 800, 1000, 1500, 2000, 3000, 4000, 6000, 8000, 20000, etc., and fats and oils include sesame oil and soybean oil. , Peanut oil, corn oil, hydrogenated oil, paraffin oil, honey beeswax and the like, and fatty acid and derivatives thereof include stearic acid, palmitic acid, myristic acid, triethyl citrate, triacetin, medium chain fatty acid triglyceride and the like.
The active substance may be dissolved in the liquid filling, but the active substance may be suspended in the liquid filling, or the liquid filling itself may be an active substance solution.

The active substance filled in the hard capsule of the present invention is not particularly limited as long as it is not toxic when used as a pharmaceutical, health food or food. For example, medicines include vitamins, antipyretics, analgesics, anti-inflammatory agents, anti-ulcer agents, cardiotonic agents, anticoagulants, hemostatic agents, bone resorption inhibitors, angiogenesis inhibitors, antidepressants, antitumor agents, antitussive expectorants Agents, muscle relaxants, antiepileptic agents, antiallergic agents, antiarrhythmic agents, vasodilators, antihypertensive diuretics, antidiabetic agents, antituberculosis agents, hormone agents, narcotic antagonists and the like.
The active substance may be liquid, and may be solid or dissolved in the liquid filling.

  Filling of the filling into the hard capsule is performed by a known capsule filling machine such as a fully automatic capsule filling machine (model name: LIQFILsuper80 / 150, manufactured by Shionogi Qualicaps Co., Ltd.), capsule filling / sealing machine (model name: LIQFILsuperFS). , Manufactured by Shionogi Qualicaps Co., Ltd.) or the like.

  According to the present invention, at the time of joining and sealing between the body part and the cap part, sealing without leaking is performed by heating the filler to be filled in the hard capsule or by using the heated filler. Hard capsules are obtained. In general, it is preferable to use a filler filled in the capsule at about 30 to 60 ° C, preferably about 30 to 45 ° C, more preferably about 35 to 40 ° C. The filling material needs to be liquid at least within the above temperature range. The temperature of the filling can be adjusted by a method known per se such as a panel heater or a hot water heater. For example, a circulating hot water heater or a seal pan unit of the integrated capsule filling / sealing machine is used as a circulating hot water heater. It is preferable to adjust with a modified model, etc., because the temperature range can be finely adjusted.

  When fitting both the body part and the cap part of the hard capsule, the fitting width in which the outer circumference of the body part and the inner circumference of the cap part overlap each other is approximately 4. About 4.0-6.0 mm is generally preferred for a 5-6.5 mm, No. 4 capsule. The sealing width is generally about 1.5 to 3.0 mm for No. 3 capsules and about 1.5 to 2.8 mm for No. 4 capsules.

  A sealing agent containing cellulose ethers is used to seal the capsule body and cap. The sealing agent is preferably in a liquid state, and may further contain a hydrophilic solvent (for example, alcohols such as ethanol) and water. The cellulose ethers that are components of the sealing agent can be exemplified by the same bases as the hard capsules described above, and preferably the same bases as the hard capsules are used. The composition of the sealing agent is generally about 10 to 25% cellulose ether, about 45 to 60% hydrophilic solvent and about 15 to 45% water, preferably about 15 to 45% cellulose ether, by weight, based on the whole sealing agent. 20%, about 50-58% hydrophilic solvent and about 25-35% water, most preferably cellulose ethers such as hydroxypropyl methylcellulose about 16%, hydrophilic solvents such as about 55% alcohols such as ethanol and The blending ratio is about 29% water.

  The sealant can be used generally at room temperature or under heating, and preferably is within a temperature range of about 23 to 45 ° C, more preferably about 23 to 35 ° C, and most preferably about 25 to 35 ° C. However, it gives good results in preventing liquid leakage of the hard capsule. The temperature of the sealant can be adjusted by a method known per se such as a panel heater or a hot water heater. For example, a circulating hot water heater or a seal pan unit of the integrated capsule filling and sealing machine is used as a circulating hot water heater type. It is preferable to adjust with a modified one, etc., because the temperature range can be finely adjusted. In addition, since alcohol, for example, ethanol in the sealant may volatilize depending on temperature conditions, it is preferable to appropriately replenish the sealant composition so that it is constant.

  The sealing of the hard capsule can be performed using a capsule filling and sealing machine known per se, such as the capsule filling and sealing machine or the capsule sealing machine (model name: HICAPSEAL 40/100, manufactured by Shionogi Qualicaps Co., Ltd.). it can.

  The hard capsules obtained by the method of the present invention have not only the advantage that there is no leakage of the filling material, and excellent operability, but also cracks due to moisture after the filling of medicines, health foods and foods, and alteration and discoloration of the filling material In addition, the capsule film is a hard capsule with excellent solubility and mechanical strength and improved appearance.

  Hereinafter, the present invention will be specifically described with reference to examples. However, the present invention is not limited thereto.

A hydroxypropylmethylcellulose capsule “QUALI-V” No. 3 white hard capsule manufactured by Shionogi Qualicaps Co., Ltd. is filled with medium-chain fatty acid triglyceride (Product name: Panacet 800, Nippon Oil & Fats Co., Ltd.) under the following filling conditions, and a hard capsule Got.
(A) Filling conditions Capsule: No. 3 white capsule Filling: Panacet 800, kinematic viscosity 18.4 cst (23.0 ° C.)
Filling speed: 15,000 capsules / hour Filling machine: LIQFILsuperFS
(B) Evaluation method The obtained hard capsules were allowed to stand on paper, and the presence or absence of liquid leakage was visually observed. The results are shown in Table 1.

As is apparent from the above table, it has been found that a hard capsule without liquid leakage can be obtained by adjusting the liquid temperature of the filling to 30 to 40 ° C., preferably 35 to 40 ° C.

  Hard capsules filled with medium-chain fatty acid triglycerides were produced in the same manner as in Example 1, and hydroxypropylmethylcellulose (16%, w / w), ethanol (55%, w / w) and water (29%, w / w) The effect of the temperature of the sealant containing) on the liquid leakage of the hard capsule was studied. The test results are shown in Table 2. However, the temperature of the sealing agent was adjusted using a circulating hot water heater.

As is apparent from Table 2 above, when the filling temperature is 35 ° C., and when the temperature of the sealing agent is about 25 to 34 ° C., none of the 4000 hard capsules leaked. It has been found. In addition, as a result of observation and inspection immediately after drying the produced hard capsule for about 10 minutes, the dry seal of the dry hard capsule has good dryness, the fitting part is kept hard, and the mechanical strength is stable. Showed sex.
In addition, the drying property in the above Table 2 was determined according to the following criteria.
X: The seal part is soft The band seal part is soft and the capsules adhere to each other at the band seal part.
Δ: Seal part is slightly soft Capsules adhere slightly, but adhering capsules come off.
○: The seal part is slightly hard The capsules do not adhere to each other, but the seal part is not sufficiently dry.
A: Hard seal part There is no adhesion between capsules, and the seal part is sufficiently dry.

  No. 3 and No. 4 hard capsules were produced under the filling conditions and sealing conditions described in Example 2, and the operability of the capsules was confirmed. The results are shown in Table 3. In the table, “transfer” means fully automatic movement of the capsule from the capsule filling part to the seal part, and “transport” means full automatic movement of the sealed capsule from the seal part to the drying device. To do.

  The method for producing a hard capsule of the present invention is useful for producing a stable hard capsule such as a medicine, health food, food, etc. that does not leak.

Is a schematic representation of the manufacturing process of the hard capsule of the present invention. Step (1) shows a separation step of the body portion and the cap portion of the hard capsule. Step (2) shows a filling step of filling the hard capsule body part. A process (3) shows the process of fitting a cap part to the hard capsule body part containing a filler. Step (4) shows a step of sealing the fitted hard capsule with a sealing agent. Step (5) shows a step of drying the sealed hard capsule.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Hard capsule cap part 2 Hard capsule body part 3 Filling material 4 Filling pipe 5 Sealing part (band seal)

Claims (11)

  Cellulose ethers characterized in that a hard capsule based on cellulose ethers is filled with a heated liquid filling, and then the body and cap portions of the capsules are sealed with a sealing agent. A method for producing hard capsules based on the above.   The method for producing a hard capsule according to claim 1, wherein the heating is adjusted so that the temperature of the liquid filling is 30 to 45 ° C.   The method for producing a hard capsule according to claim 1, wherein the heating is performed so that the temperature of the liquid filling is 35 to 40 ° C.   The method for producing a hard capsule according to any one of claims 1 to 3, wherein the sealant contains cellulose ethers.   The method for producing a hard capsule according to any one of claims 1 to 4, wherein the sealing agent further contains a hydrophilic solvent and water.   The sealing agent contains cellulose ethers 10 to 25%, alcohols 45 to 60% and water 15 to 45% by mass% with respect to the whole sealing agent, according to any one of claims 1 to 5. The manufacturing method of the hard capsule of description.   The temperature of a sealing agent is 23-45 degreeC, The manufacturing method of the hard capsule in any one of Claims 1-6 characterized by the above-mentioned.   The temperature of a liquid filling is 30-45 degreeC, and the temperature of a sealing agent is 23-45 degreeC, The manufacturing method of the hard capsule in any one of Claims 1-7 characterized by the above-mentioned.   The hard capsule which can be manufactured by the method in any one of Claims 1-8.   Liquid capsule filled with liquid filler in a hard capsule based on cellulose ethers, and the capsule body part and the cap part are sealed with a sealing agent containing cellulose ethers. Agent. A sealing agent for hard capsules comprising 10 to 25% of cellulose ethers, 45 to 60% of alcohols and 15 to 45% of water by mass% with respect to the whole sealing agent.